Apparatus and method for thermal assisted desorption ionization systems

ABSTRACT

The present invention is directed to a method and device to desorb an analyte using heat to allow desorption of the analyte molecules, where the desorbed analyte molecules are ionized with ambient temperature ionizing species. In various embodiments of the invention a current is passed through a mesh upon which the analyte molecules are present. The current heats the mesh and results in desorption of the analyte molecules which then interact with gas phase metastable neutral molecules or atoms to form analyte ions characteristic of the analyte molecules.

PRIORITY CLAIM

This application is a continuation of (1) U.S. patent application Ser.No. 15/942,162 entitled “APPARATUS AND METHOD FOR THERMAL ASSISTEDDESORPTION IONIZATION SYSTEMS”, inventors: Jordan Krechmer and Brian D.Musselman, filed Mar. 30, 2018, which is a continuation of (2) U.S.patent application Ser. No. 15/368,490 entitled “APPARATUS AND METHODFOR THERMAL ASSISTED DESORPTION IONIZATION SYSTEMS”, inventors: JordanKrechmer and Brian D. Musselman, filed Dec. 2, 2016, which issued asU.S. Pat. No. 9,960,029 on May 1, 2018, which is a continuation of (3)U.S. patent application Ser. No. 14/876,677 entitled “APPARATUS ANDMETHOD FOR THERMAL ASSISTED DESORPTION IONIZATION SYSTEMS”, inventors:Jordan Krechmer and Brian D. Musselman, filed Oct. 6, 2015 which issuedas U.S. Pat. No. 9,514,923 on Dec. 6, 2016, which is a continuation of(4) U.S. patent application Ser. No. 14/589,687 entitled “APPARATUS ANDMETHOD FOR THERMAL ASSISTED DESORPTION IONIZATION SYSTEMS”, inventors:Jordan Krechmer and Brian D. Musselman, filed Jan. 5, 2015 which issuedas U.S. Pat. No. 9,224,587 on Dec. 29, 2015, which is a continuation of(5) U.S. patent application Ser. No. 14/455,611 entitled “APPARATUS ANDMETHOD FOR THERMAL ASSISTED DESORPTION IONIZATION SYSTEMS”, inventors:Jordan Krechmer and Brian D. Musselman, filed Aug. 8, 2014 which issuedas U.S. Pat. No. 8,963,101 on Feb. 24, 2015 and which is a continuationof and claims priority to (6) U.S. patent application Ser. No.13/364,322 entitled “APPARATUS AND METHOD FOR THERMAL ASSISTEDDESORPTION IONIZATION SYSTEMS”, inventors: Jordan Krechmer and Brian D.Musselman, filed Feb. 2, 2012 which issued as U.S. Pat. No. 8,822,949 onSep. 2, 2014, and which claims priority to (7) U.S. Provisional PatentApplication No. 61/439,866 entitled “APPARATUS FOR THERMAL ASSISTEDDESORPTION IONIZATION”, inventors Jordan Krechmer and Brian D.Musselman, filed Feb. 5, 2011; (8) U.S. Provisional Patent ApplicationNo. 61/582,204 and entitled “APPARATUS AND METHOD FOR THERMAL ASSISTEDDESORPTION IONIZATION SYSTEMS” by, inventors Jordan Krechmer and BrianD. Musselman, filed Dec. 30, 2011, and (9) U.S. Provisional PatentApplication No. 61/587,218 and entitled “APPARATUS AND METHOD FORTHERMAL ASSISTED DESORPTION IONIZATION SYSTEMS”, inventors JordanKrechmer and Brian D. Musselman, filed Jan. 17, 2012. The presentapplication is related to (10) U.S. patent application Ser. No.13/797,409 entitled “APPARATUS AND METHOD FOR THERMAL ASSISTEDDESORPTION IONIZATION SYSTEMS”, inventors: Jordan Krechmer and Brian D.Musselman, filed Mar. 12, 2013 which issued as U.S. Pat. No. 8,754,365on Jun. 17, 2014. The contents of each of (1)-(10) are herein expresslyincorporated by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates to methods and devices for controlling thekinetic energy and/or the efficiency of desorption of neutral moleculesfrom a surface.

BACKGROUND OF THE INVENTION

The present invention relates to methods and devices for controlling thekinetic energy and/or the efficiency of desorption of neutral moleculesfrom a surface. The present invention relates to methods and devices forcontrolling the kinetic energy and/or the efficiency of desorption ofneutral molecules from a surface Development of devices for desorptionionization of molecules direct from solids, and liquids in open airusing a direct analysis in real time (DART) source has previously beendescribed in U.S. Pat. No. 6,949,741 “Atmospheric Pressure IonizationSource” which is expressly incorporated by reference in its entirety.DART uses a heated carrier gas to effect desorption of sample into thatsame carrier gas where gas phase ionization occurs. Unfortunately, theheating of the carrier gas to a sufficient temperature to enabledesorption of some analytes takes considerable time. Further, thetransfer of heat to the sample by that gas is not very efficient. A gasion separator described in U.S. Pat. No. 7,700,913, “Sampling system foruse with surface ionization spectroscopy” which is expresslyincorporated by reference in its entirety can be used to improve theefficiency of sampling.

SUMMARY OF THE INVENTION

The present invention relates to methods and devices for controlling thekinetic energy and/or the efficiency of desorption of neutral moleculesfrom a surface. In various embodiments of the present invention, a meshcan be placed between the source of ionizing gas, which can be atatmospheric pressure, and the inlet of a spectrometer. The mesh can bemade from a conductive material and can carry an electrical current. Inan embodiment of the invention a sample can be deposited directly ontothe mesh. A current can be applied to the mesh in order to heat thewire. Sample related molecules can be desorbed from or in closeproximity to the mesh. The desorbed molecules can interact with theionizing gas in the region between the mesh and the atmospheric pressureionization (API)-inlet of a spectrometer. The ions that are formed fromthis interaction can enter the spectrometer for analysis. In anembodiment of the present invention, the desorbed molecules can enterthe high pressure region of a spectrometer by the action of anelectrical field as in the case of an ion mobility spectrometer (IMS).The ions formed in the region immediately adjacent to the wire meshwhich in this case has a potential equivalent to the end of the IMSenter the IMS spectrometer for analysis.

In various embodiments of the present invention, a mesh can be placedbetween the source of ionizing gas, which can be at atmosphericpressure, and the inlet of a spectrometer. The mesh can be made from aconductive material and can carry an electrical current. In variousembodiments of the invention a sample can be deposited directly onto themesh. A current can be applied to the mesh in order to heat the wiredesorbing ions and neutrals of the sample into the atmospheric pressureregion.

Sample related molecules can be desorbed from or in close proximity tothe mesh. The desorbed molecules can interact with the ionizing gas inthe region between the mesh and the atmospheric pressure ionization(API)-inlet of a spectrometer. The ions that are formed near to the wiremesh from this interaction can enter the spectrometer for analysis atatmospheric pressure or at a pressure that are higher than atmosphericwhen electrical potentials are able to draw or push those ions into thevolume of the spectrometer.

In various embodiments of the present invention, two or more mesh can beplaced between the source of ionizing gas, which can be at atmosphericpressure, and the inlet of a spectrometer. The two or more mesh can bemade from a conductive material and can carry an electrical current. Invarious embodiments of the invention two or more samples can bedeposited directly onto two or more of the mesh. A current can beapplied to the two or more of the sample containing mesh in order toheat the wire mesh desorbing ions and neutrals into the atmosphericpressure region. The kinetic energy of ions desorbed from or in closeproximity to the wire mesh can be controlled by modulating the potentialapplied to adjacent mesh or series of mesh. Control of the ion kineticenergy in the region between the sample laden wire mesh and theatmospheric pressure ionization (API)-inlet of a spectrometer can beused to improve the analysis of the two or more samples. Control of theion kinetic energy in the region between the sample laden wire mesh andthe atmospheric pressure ionization (API)-inlet of a spectrometer isdesirable to improve the resolution of the spectrometer. The ions thatare formed from this interaction can enter the spectrometer foranalysis.

The kinetic energy of ions desorbed from or in close proximity to thewire mesh can be controlled by modulating the potential applied to theadjacent mesh or series of mesh. Control of the ion kinetic energy inthe region between the sample laden wire mesh and the atmosphericpressure ionization (API)-inlet of a spectrometer can be used to improvethe transfer of ions into the spectrometer for analysis of the one ormore samples. Application of an electrical potential to the wire meshenables limited control of the ion kinetic energy in the region betweenthe sample laden wire mesh and the atmospheric pressure ionization(API)-inlet of a spectrometer which can have either a differentelectrical potential applied to its surface or be operated at the samepotential as that wire mesh. Depending on the configuration of thespectrometer inlet the application of a potential can be used to improveresolution of the spectrometer. The ions that are formed near to thewire mesh can enter the spectrometer for analysis at atmosphericpressure or at a pressure that are higher than atmospheric whenelectrical potentials are able to draw or push those ions into thevolume of the spectrometer.

In various embodiments of the invention, in order to control the ionenergy of ions entering an ion mobility spectrometer the wire meshsupporting the ionization can be placed immediately in front of the wiremesh to which potential is being applied in order to control ion kineticenergy. In the case of ion mobility spectrometers it can be necessary tointroduce ions at or very close to the potential of at the IMS entrancein order for the ions to enter and be retained by the spectrometer.

In traditional IMS devices ionization of neutral molecules occurs in thevolume of the spectrometer. Ions are generated using radioactiveparticle emission from elements such as ³H (tritium), ⁶³Ni, or otherradioactive materials. Plasma-based ionization is also feasible usingelectrical discharge in the volume of the sampling region in order toproduce ions which subsequently interact with the neutral molecules toionize them in that volume. The production of ions inside of the volumeof the IMS reduces the range of ion kinetic energies for the ionizedparticles since the electrical field is uniform in that region ofionization.

The position of the ionization source relative to the IMS determines adistance over which ions trajectory must follow before entering the IMS.Positioning of the IMS ionization region even a very short distance awayfrom the entrance to the spectroscopy system results in a decline inachievable resolution of the spectroscopy system. In the case of ambientpressure ionization from a heated wire mesh, rapid vaporization of thesample into the carrier gas from the sample laden wire mesh can occur inclose proximity to the entrance of the IMS between the carrier gassource, and the inlet of the IMS spectroscopy system. Thus the positionof the sample laden wire mesh relative to the entrance of the IMSspectrometer influences the kinetic energy of the ions formed from thosedesorbed molecules. The kinetic energy distribution of ions that areformed immediately in the vicinity of the wire mesh in close proximityto the IMS can be corrected. As the majority of ions produced in theexperiment are produced at or near atmospheric pressure in closeproximity to the wire mesh those ions may be formed inside the volume ofthe ion mobility spectrometer (IMS). The kinetic energy of ions isrelated to the electrical fields in which they are formed. In the caserof the IMS systems the kinetic energy is thought to be uniform when allions are formed inside the tube, however in order to effect sampling ofions for spectroscopic analysis a potential is applied to wires thatform a Bradbury-Nielson gate a short distance away from the he ionizingregion. The distance between the BN-gate and the position where the ionsare formed effects their kinetic energy. The ability to change theenergy of the ions formed in very close proximity to the IMS entranceimproves the control of those ions afforded by the ion focusing of theIMS. Application of a electrical potential to the wire mesh in closeproximity to the ionization region therefore will change the ion kineticenergy of those ions that are closer to the wire mesh to a greaterdegree than those that have been formed further away from the wire mesh.Linking the application of electrical potential applied to the wire meshwith the electrical potential used to open and close the BN-gate enablesthose ions that are further from the gate to catch up to the ions thatare closer thus generating a collection of ions that have a more uniformkinetic energy as they are transferred from the ionization region intothe ion separation region of the spectrometer.

In an embodiment of the invention application of a potential to a wiremesh located between a wire mesh from which sample molecules are beingdesorbed and the entrance the spectrometer to which a differentpotential applied is used to change the kinetic energy of ions formed inclose proximity to that wire mesh.

In an alternative embodiment of the invention application of a smallpotential to the kinetic energy controlling mesh will result inrejection of the ions by the spectrometer. The action of rejection ionswhose kinetic energy is different than those ions formed inside theatmospheric pressure region of the spectrometer can be used to furtherimprove the resolution of the spectrometer as it reduces the kineticenergy of the ions being sampled.

In various embodiments of the invention, in order to complete a morerapid vaporization of the sample into the carrier gas the sample ladenmesh can be positioned between the carrier gas source, a gas ionseparator and the atmospheric pressure inlet of a spectroscopy system.

In an alternative embodiment of the invention a sample can be depositedonto a second surface that can be placed in close proximity to the meshthrough which the ionizing carrier gas can flow. Sample relatedmolecules can be desorbed from the second surface as a result of thecurrent applied to the mesh. Sample related molecules can be desorbedfrom the second surface as a result of heating of the mesh by increasingthe current running through the mesh. In various embodiments of theinvention, by increasing the current passed through the wire, increasedradiant heating can be generated. In various embodiments of theinvention, increased radiant heat can effect desorption of less volatilecomponents in a sample.

In an alternative embodiment of the invention a chemical can bedeposited onto a second surface that can be placed in close proximity tothe mesh through which the ionizing carrier gas can flow. Molecule ofthat chemical can be desorbed from the second surface as a result of thecurrent applied to the mesh. In various embodiments of the invention, byincreasing the current passed through the wire, increased radiantheating can be generated resulting in vaporization of the chemical intothe ionizing region where it might be ionized creating an ion that mightionize other molecules. In various embodiments of the invention, thechemical desorbed from the second surface acts as a dopant for ionizingsample related molecules.

BRIEF DESCRIPTION OF THE DRAWINGS

This invention is described with respect to specific embodimentsthereof. Additional aspects can be appreciated from the Figures inwhich:

FIG. 1 is a schematic diagram of a sampling probe including a heatedfilament for sample desorption positioned between a source for ionizinggas and the atmospheric pressure inlet of a spectrometer;

FIG. 2 is a schematic diagram of a sampling system incorporating themesh as a sample support for desorption ionization positioned between asource for ionizing gas and a gas ion separator positioned before theatmospheric pressure inlet of a spectrometer, according to an embodimentof the invention;

FIG. 3 is a schematic diagram of a sampling system incorporating a powersupply to heat the mesh positioned between the ionizing gas source and agas ion separator where analyte has been placed on the mesh;

FIG. 4(A) shows a partial mass chromatogram of the 325 Dalton ionproduced during analysis and FIG. 4(B) shows the mass spectrumcontaining the molecular ion for quinine at 325 Daltons obtained using aDART carrier gas temperature of 50 degrees Centigrade while rapidlyincreasing the current passing through the mesh supporting the samplefrom 0 Amps at time=0, to 6 Amps at time=30 seconds;

FIG. 5A is a mass spectrum of a sample of Extra Virgin Olive oilacquired using a thermal assisted DART source with carrier gastemperature of 50 degrees Centigrade and a current of approximately 4.5Amps applied to the mesh according to an embodiment of the invention;

FIG. 5B is a mass spectrum of a sample of Extra Virgin Olive oilacquired using a thermal assisted DART source with carrier gastemperature of 50 degrees Centigrade and a current of approximately 6.5Amps applied to the mesh according to an embodiment of the invention;

FIG. 6 is a schematic diagram of a sampling system incorporating anionizing gas source, a mesh with a porous material applied to the mesh,a power supply to heat the mesh according to an embodiment of theinvention;

FIG. 7 is a schematic diagram of a sampling system incorporating anionizing gas source with two mesh pieces with independent powersupplies, wherein the meshes are positioned between the ionizing gassource and the sample to be analyzed where the sample is positioned inclose proximity to a gas ion separator which permits transfer of ions tothe API-inlet region of the mass spectrometer according to an embodimentof the invention;

FIG. 8 is a schematic diagram of a sampling system incorporating anionizing gas source with two mesh pieces heated with a single powersupply, wherein the meshes are positioned between the ionizing gassource and the sample to be analyzed where the sample is positioned inclose proximity to a gas ion separator which permits transfer of ions tothe API-inlet region of the mass spectrometer according to an embodimentof the invention;

FIGS. 9A, B, C and D are schematic diagrams of a sampling systemincorporating an ionizing gas source with a mesh associated with a cardand a reservoir, wherein the mesh is positioned between the ionizing gassource and a gas ion separator which permits transfer of ions to theAPI-inlet region of the mass spectrometer according to an embodiment ofthe invention;

FIG. 10 shows a drawing of a foam sponge plastic attached to a mesh,according to an embodiment of the invention;

FIG. 11 shows a drawing of the liquid sample being applied to a foamsponge plastic attached to a mesh associated with a card, according toan embodiment of the invention;

FIG. 12 shows a drawing of Oolong tea leaves enclosed in the mesh troughassociated with a card, according to an embodiment of the invention;

FIG. 13 shows a drawing of the foam sponge plastic attached to a meshassociated with a card which can be heated by a power supply, whereinthe foam sponge plastic and the mesh are positioned between the ionizinggas source and a gas ion separator, according to an embodiment of theinvention;

FIG. 14(A) shows a total ion chromatogram (TIC) over the time intervalzero to two minutes obtained using a DART carrier gas temperature of 50degrees Centigrade while rapidly increasing the current passing throughthe mesh supporting the sample applied to a foam sponge plastic from 0Amps at time=0, to 6 Amps at time=30 second; FIG. 14(B) shows a partialmass chromatogram of the 195 Dalton ion produced during the two minuteanalysis shown in FIG. 14(A); and FIG. 14(C) shows the mass spectrumobtained by summing the spectra obtained between 0.68-1.08 minutes ofthe TIC shown in FIG. 14A;

FIG. 15 shows a drawing of the two mesh associated with a card,according to an embodiment of the invention;

FIG. 16 shows the mass spectrum obtained from a sample of Oolong tealeaves enclosed in a mesh trough associated with a card which was heatedby a power supply according to an embodiment of the invention;

FIG. 17 shows a conventional DART mass spectrum obtained from a sampleof Oolong tea leaves;

FIG. 18 shows a drawing of the two mesh associated with a cardpositioned in close proximity to the API-inlet region of a massspectrometer, according to an embodiment of the invention;

FIG. 19 shows the mass spectrum obtained from a sample of olive oil intoluene applied to a mesh and ammonia applied to second mesh, whereinboth mesh are associated with a card which was heated by a single powersupply (not shown), according to an embodiment of the invention;

FIG. 20 shows the mass spectrum obtained from a sample of olive oil intoluene applied to a mesh associated with a card which was heated by apower supply; and

FIG. 21 shows a drawing of the mesh trough associated with a card,according to an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION Definitions

The transitional term “comprising” is synonymous with “including,”“containing,” or “characterized by,” is inclusive or open-ended and doesnot exclude additional, unrecited elements or method steps.

The transitional phrase “consisting of” excludes any element, step, oringredient not specified in the claim, but does not exclude additionalcomponents or steps that are unrelated to the invention such asimpurities ordinarily associated with a composition.

The transitional phrase “consisting essentially of” limits the scope ofa claim to the specified materials or steps and those that do notmaterially affect the basic and novel characteristic(s) of the claimedinvention.

A vacuum of atmospheric pressure is 1 atmosphere=760 torr. Generally,‘approximately’ in this pressure range encompasses a range of pressuresfrom below 10¹ atmosphere=7.6×10³ torr to 10⁻¹ atmosphere=7.6×10¹ torr.A vacuum of below 10⁻³ torr would constitute a high vacuum. Generally,‘approximately’ in this pressure range encompasses a range of pressuresfrom below 5×10⁻³ torr to 5×10⁻⁶ torr. A vacuum of below 10⁻⁶ torr wouldconstitute a very high vacuum. Generally, ‘approximately’ in thispressure range encompasses a range of pressures from below 5×10⁻⁶ torrto 5×10⁻⁹ torr. In the following, the phrase ‘high vacuum’ encompasseshigh vacuum and very high vacuum. The prime function of the gas ionseparator is to remove the carrier gas while increasing the efficiencyof transfer of neutral molecules including analyte molecules into themass spectrometer. When constructed from non conducting material, thegas ion separator can also be used to insulate or shield the highvoltage applied to the inlet of the mass spectrometer.

A filament means one or more of a loop of wire, a segment of wire, ametal ribbon, a metal strand or an un-insulated wire, animal string,paper, perforated paper, fiber, cloth, silica, plastic, plastic foam,polymer, teflon, polymer impregnated teflon, cellulose and hydrophobicsupport material coated and impregnated filaments.

A metal comprises one or more elements consisting of lithium, beryllium,boron, carbon, nitrogen, oxygen, sodium, magnesium, aluminum, silicon,phosphorous, sulphur, potassium, calcium, scandium, titanium, vanadium,chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium,germanium, arsenic, selenium, rubidium, strontium, yttrium, zirconium,niobium, molybdenum, technetium, ruthenium, rhodium, palladium, silver,cadmium, indium, tin, antimony, tellurium, cesium, barium, lanthanum,cerium, praseodymium, neodymium, promethium, samarium, europium,gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium,lutetium, hafnium, tantalum, tungsten, rhenium, osmium, iridium,platinum, gold, mercury, thallium, lead, bismuth, polonium, francium andradium.

A plastic comprises one or more of polystyrene, high impact polystyrene,polypropylene, polycarbonate, low density polyethylene, high densitypolyethylene, polypropylene, acrylonitrile butadiene styrene, polyphenylether alloyed with high impact polystyrene, expanded polystyrene,polyphenylene ether and polystyrene impregnated with pentane, a blend ofpolyphenylene ether and polystyrene impregnated with pentane orpolyethylene and polypropylene.

A polymer comprises a material synthesized from one or more reagentsselected from the group comprising of styrene, propylene, carbonate,ethylene, acrylonitrile, butadiene, vinyl chloride, vinyl fluoride,ethylene terephthalate, terephthalate, dimethyl terephthalate,bis-beta-terephthalate, naphthalene dicarboxylic acid, 4-hydroxybenzoicacid, 6-hyderoxynaphthalene-2-carboxylic acid, mono ethylene glycol (1,2ethanediol), cyclohexylene-dimethanol, 1,4-butanediol, 1,3-butanediol,polyester, cyclohexane dimethanol, terephthalic acid, isophthalic acid,methylamine, ethylamine, ethanolamine, dimethylamine, hexamthylaminediamine (hexane-1,6-diamine), pentamethylene diamine,methylethanolamine, trimethylamine, aziridine, piperidine,N-methylpiperideine, anhydrous formaldehyde, phenol, bisphenol A,cyclohexanone, trioxane, dioxolane, ethylene oxide, adipoyl chloride,adipic, adipic acid (hexanedioic acid), sebacic acid, glycolic acid,lactide, caprolactone, aminocaproic acid and or a blend of two or morematerials synthesized from the polymerization of these reagents.

A plastic foam means a polymer or plastic in which a bubble containing agas is trapped including polyurethane, expanded polystyrene, phenolicfoam, XPS foam and quantum foam.

A mesh means one or more of two or more connected filaments, two or moreconnected strings, foam, a grid, perforated paper, screens, paperscreens, plastic screens, fiber screens, cloth screens, polymer screens,silica screens, Teflon screens, polymer impregnated Teflon screens,cellulose screens and hydrophobic support material coated or impregnatedmesh. In various embodiments of the invention, a mesh includes one ormore of three or more connected filaments, three or more connectedstrings, mesh, foam, a grid, perforated paper, screens, plastic screens,fiber screens, cloth and polymer screens.

Deployed means attached, affixed, adhered, inserted, located orotherwise associated. Thus a paper screen can be deployed on a cardwhere the paper for the screen and the paper for the card are of aunitary construction. A card means a sample holder. A card can be madeof one or more of paper, cardboard, insulating materials, conductivematerials, plastic, polymers, minerals and metals. A reservoir is avessel used to contain one or more of a liquid, a gas or a solid sample.

In the following description, various aspects of the present inventionwill be described. However, it will be apparent to those skilled in theart that the present invention may be practiced with only some or allaspects of the present invention. For purposes of explanation, specificnumbers, materials, and configurations are set forth in order to providea thorough understanding of the present invention. However, it will beapparent to one skilled in the art that the present invention may bepracticed without the specific details. In other instances, well-knownfeatures are omitted or simplified in order not to obscure the presentinvention.

Parts of the description will be presented in data processing terms,such as data, selection, retrieval, generation, and so forth, consistentwith the manner commonly employed by those skilled in the art to conveythe substance of their work to others skilled in the art. As is wellunderstood by those skilled in the art, these quantities (data,selection, retrieval, generation) take the form of electrical, magnetic,or optical signals capable of being stored, transferred, combined, andotherwise manipulated through electrical, optical, and/or biologicalcomponents of a processor and its subsystems.

Various operations will be described as multiple discrete steps in turn,in a manner that is most helpful in understanding the present invention;however, the order of description should not be construed as to implythat these operations are necessarily order dependent.

Various embodiments will be illustrated in terms of exemplary classesand/or objects in an object-oriented programming paradigm. It will beapparent to one skilled in the art that the present invention can bepracticed using any number of different classes/objects, not merelythose included here for illustrative purposes.

The invention is illustrated by way of example and not by way oflimitation in the figures of the accompanying drawings in which likereferences indicate similar elements. It should be noted that referencesto ‘an’ or ‘one’ embodiment in this disclosure are not necessarily tothe same embodiment, and such references mean at least one.

There remain encumbrances to the employment of the DART technique for avariety of samples and various experimental conditions. Previously, inorder to facilitate more comprehensive analysis of samples the DARTdesorption ionization method utilized heating of the carrier gas, whichcontains the metastable species. As the carrier gas temperature wasincreased molecules were vaporized where interaction with the metastablespecies resulted in ionization of the molecules. This transfer of energyusing heated gas limits the efficiency of the analysis process. Itresults in consumption of large volumes of gas and more significantlyadds a significant delay to the time taken for the analysis. The timerequired to increase the carrier gas temperature by three hundreddegrees can be several minutes. In contrast, the time required forcollection of the mass spectrum at the optimum temperature can be asshort as a second. Enabling more efficient heating using a metalsubstrate often results in an increase in thermal decomposition of thematerial of interest. Likewise, employing more efficient heating of thecarrier gas is difficult to achieve without negatively affecting themetastable species present in the carrier gas.

In various embodiments of the invention placing sample on a poroussurface directly in the path of the carrier gas such that the gas flowsthrough it, the so called “transmission-DART” configuration results in amethod that does not require heating of the ionizing gas. In variousembodiments of the invention, the transmission-DART configurationresults in less thermal degradation of the analyte prior to gas phaseionization. In various embodiments of the invention, thetransmission-DART configuration results in generation of mass spectrawith fewer ions derived from thermal decomposition of the sample thanobserved in conventional open air ionization experiments. In variousembodiments of the invention, the transmission-DART configuration usessignificantly lower volumes of gas carrier during the experiment. Invarious embodiments of the invention, the transmission-DARTconfiguration reduces the function of the carrier gas to providing themetastable species for ionization. In various embodiments of theinvention, the transmission-DART configuration heats the porous surfaceby directing electrical current through a mesh in close proximity to theporous surface which transfers heat to the sample. In variousembodiments of the invention, the transmission-DART configuration lowersthe carrier gas temperature enabling an increase in spatial resolutionof the analysis since only molecules from the heated region vaporize. Invarious embodiments of the invention, the transmission-DARTconfiguration allows direct heating of specific regions of the mesh tofacilitate higher throughput analysis since samples can be placed incloser proximity to each other. In various embodiments of the invention,the application of the transmission-DART configuration to heating ofporous surfaces results in more rapid desorption than available by theconventional DART experiment.

In various embodiments of the invention the sample is deposited on asecond surface in close proximity to the mesh in order for the heatgenerated from the application of current to the mesh to causedesorption of molecule from that sample into the gas phase whereionization occurs.

In an alternative embodiment of the present invention, separate aliquotsof the sample are placed on separate mesh pieces and placed in closeproximity to one another in the presence of the same ionizing gas inorder that the temperature of the gas and the temperature of theunheated mesh simultaneously increase to effect desorption of moleculesinto the gas phase for analysis of the sample. In various embodiments ofthe invention the mesh is surrounded by a porous material to whichsample has been applied for analysis. After positioning the sample inthe region between the ionizing gas source and the inlet of thespectrometer a current is applied to the mesh to complete heating of thesurrounding material and desorption of molecules into the gas phase forionization.

Direct Ionization in Real Time (DART) (Cody, R. B., Laramee, J. A.,Durst, H. D. “Versatile New Ion Source for the Analysis of Materials inOpen Air under Ambient Conditions” Anal. Chem., 2005, 77, 2297-2302 andDesorption Electrospray Surface Ionization (DESI) (Cooks, R. G., Ouyang,Z., Takats, Z., Wiseman., J. M. “Ambient Mass Spectrometry”, Science,2006, 311, 1566-1570; both articles are herein explicitly incorporatedby reference in their entireties, are recent developments enablingsurface desorption ionization by producing ions in open air fordetection with mass spectrometer systems. Since the invention of DART avariety of gas-based open air ionization systems have been demonstratedincluding but not limited to, Plasma Assisted Desorption/Ionization alsoknown as Dielectric Barrier Discharge Ionization (PADI, DBDI or DCBI),Desorption Atmospheric Pressure Chemical Ionization (DAPCI), DesorptionSonic Spray Ionization (DeSSI), Desorption Atmospheric PressurePhotoionization (DAPPI), and Flowing Atmospheric-Pressure Afterglow(FAPA). The ability to desorb and ionize intact molecules in open airoffers a number of advantages for rapid real time analysis of analytesamples. In the case of the DART ionization source, the ability to varythe carrier gas temperature has been used to permit thermal profiling ofsamples. This application of heat has permitted a more thoroughdetection of the various components of the sample. This is especiallytrue when the components of the sample have different vapor pressure.Unfortunately due to the resistive character of heaters and the largevolume of gas that these methods use to transfer heat into the sample,operation at high temperature involves a number of limitations. Forexample, waiting for the temperature of the gas exiting the source toincrease to a desired temperature can take several minutes slowing theanalysis of sample considerably.

Determination of the chemical composition of solid objects or materialspresent on the surface of those objects is facilitated by removing thosematerials to a chemical analyzer. Methods for removing chemicals fromthe surface include the use of heated gas, heat source capable ofradiating heat to the surface, application of liquid such as water orsolvents to dissolve chemicals present on or comprising the surface. Invarious embodiments of the invention it is desirable to desorb neutralmolecules from a surface by using jets supplying steam or heated water.In various embodiments of the invention, it is desirable to apply avacuum in the vicinity of the surface to remove the desorbed neutralmolecules released from the surface. This combination combines theaction of heated water vapor desorbing material from the surface whilealso applying suction to quickly remove the vapor from the surface areathus avoiding condensation of the liquid back onto the surface.

A problem in chemical analysis is that the use of water can damage manychemical sensors therefore generally speaking the water vapor iscondensed and used in the liquid form. For reasons associated withimproved analysis throughput and the determination of chemicals thatmight be present on surfaces that are porous, such as baggage, clothing,cardboard and inside of packaging that might be sealed for purposes ofprotecting the chemicals inside from analysis a directed jet of heatedwater vapor or steam can be used to remove molecules from surfaces or inthe immediate proximity of surfaces in order to achieve a throughchemical analysis.

In many cases containers carrying illicit materials such as narcotics orfood are packaged in plastic so as to prevent exposure to liquid orother chemicals. Plastic packaging is not thought to be permeable,however owing to the need to keep the material flexible small moleculesdefined as plasticizers are an integral part of the composition of thatpackaging material. The use of plasticizers effectively means that thereis a liquid component of the plastic that may move freely from oneinside the container to outside the container. Movement of a moleculefrom one surface to another and back again can be driven by alternatinghot and cold treatments to increase the movement of molecules. Whileplasticizers are generally thought of as inert molecules, they containfunctional chemical subunits that are capable of binding and releasingchemicals that they come into contact with, even when the contact periodis a short period of time. In various embodiments of the invention, apulsed jet of heated water vapor can be directed at the outside surfaceof a plastic package to interrogate the composition of the contents ofthe plastic package.

In the case of a customs inspection, some chemicals are deemed to be toodangerous to open. Simple economics prevail and often high valuechemicals are mislabeled for import to save on duties. The capability toessentially extract an infinitesimal volume of sample with a benignsampling protocol can aid these investigators. In various embodiments ofthe invention, a jet of heated water vapor can be directed at theoutside surface of a plastic package to interrogate the composition ofthe contents of the plastic package.

Determination of Fatty Acid Content of Triacyl-Glycerides

A method for direct formation of methyl-esters in the heated injector ofa gas chromatography instrument demonstrated the potential for bypassingthe time consuming saponification step. The experiment incorporatedmixing a chemical reagent, tetramethyl ammonium hydroxide, with theanalyte followed by injection into the heated volume of the GC injectorleading to a simultaneous hydrolysis of the acid and its methylation, atrans-esterification. In an embodiment of the invention alternatereactants can be used for direct formation of methyl-esters includingbut not limited to boron trifluoride in methanol, tetramethyl ammoniumchloride and similar reagents commonly used for the trans-esterificationof fatty acids.

In an embodiment of the invention, a triacyl-glyceride containing sampleis combined with a methylating reagent in open air on a conductingscreen which can be rapidly heated by application of an electric currentto the screen. Rapid heating of the screen as inert carrier gascontaining metastable helium atoms flow through the screen leads todesorption of the reaction products into the vapor phase whereionization occurs. The use of inert gas results in generation ofprotonated molecules of the fatty acid methyl esters. The reactionproducts can be detected in seconds using a mass spectrometer.

In an embodiment of the invention, determination of the type andpercentage of fatty acids present in the original sample can beaccomplished by measuring the relative ratios of each fatty acid methylester. This can typically be carried out by introducing isotopicallylabeled fatty acids to the original reaction mixture prior to heatingand desorption ionization. While the relative ionization potential ofindividual fatty acid methyl esters may vary, the use of these standardswill serve to provide correction coefficients for use in assigning therelative ratio of the fatty acids present in the mixture.

Thermal desorption of samples in the DART carrier gas stream can becarried out using a heated filament. This technique can produce ionscharacteristic of the analyte molecules present in the sample. As shownin FIG. 1, sample analysis can be completed by applying a small amountof sample onto a probe (102) with a filament at its distal end (128) andinserting the filament into the gap between the DART source (101) andthe API-inlet of the mass spectrometer (152). A variable current powersupply (160) can be used to heat the wire and desorb analyte molecules.The resulting mass spectrum contains the ions typically observed for theDART experiment however placing the filament in close proximity to theatmospheric pressure inlet resulted in a weak signal which wasconsistent with dramatically lowered and therefore unstable ionproduction. As unstable ion current can have a deleterious effect onboth reproducibility and sensitivity the approach was inadequate for usein quantitative analysis and detection of trace contaminants whichrequire stable background for signal processing.

In order to address the issue of instability caused by the electricalfield in the desorption ionization region a large format mesh (216)inserted in a mesh holder (290) can be placed in the region between theDART source (201) and the API inlet of the mass spectrometer (252) and agas ion separator used as an insulator/isolator (234). A gas ionseparator is a device that can improve the signal to noise ratio of DARTionization. The gas ion separator can consist of a short length oftubing placed between the desorption ionization region at the distal endof the DART source and the API inlet of the spectrometer. The gas ionseparator can be used to transport ions to the API-inlet. However as itcan also act in this experiment as an electrical insulator or isolator.In various embodiments of the invention shown in FIG. 2, a gas ionseparator (234) can be positioned between the mesh (216) and theAPI-inlet of the mass spectrometer (252) resulting in increased ionproduction while not limiting the amount of carrier gas introduced intothe spectrometer. The implementation of this experimental configurationdiminished the instability by increasing the distance between the metalof the wire to which the sample was applied and the metal surface of theatmospheric pressure inlet (252), which often carries a high electricpotential. The mass spectra acquired by using a direct probe inserted inthe gap between the DART source and the API-inlet of the massspectrometer can therefore be stabilized by using the gas ion separator(234).

The experimental configuration where the mesh is loaded with sample andplaced between the DART source and API inlet of the mass spectrometerdetector is referred to as the ‘Transmission DART’ mode. In variousembodiments of the invention, the heated ionizing carrier gas flowsthrough and across the mesh surface rather than around it. In variousembodiments of the invention, Transmission DART promotes desorptionionization and detection of molecules with good sensitivity. Theobservation that ionization was possible at lower carrier gastemperature when using the mesh compared to desorption directly from anon-conducting surface as in conventional DART, i.e., with desorptionfrom a glass capillary tube led to the design of a rapid heating system.

In various embodiments of the invention, shown schematically in FIG. 3 aheated carrier gas exits a DART source (301) and contacts a samplecoated onto a mesh (316). The mesh (316) can be positioned between thesource (301) and the proximal end of a gas ion separator (334) capableof transporting ions produced from that sample to the sampling region ofan atmospheric pressure inlet of the mass spectrometer. Separateelectrical leads from the positive and negative terminals of a variablecurrent, low voltage power supply (360) can be connected to oppositesides of the wire grid in order to supply an electric current throughthe mesh.

In various embodiments of the invention, positioning a sample stagecomprised of a mesh placed in-line between the exit of the DART sourceand the API inlet of the spectrometer enables Thermally Assistedionization of analytes using DART, (TA-DART). In various embodiments ofthe invention, using the DART source with room temperature carrier gasand passing approximately 1-7 Amps of current through the mesh resultedin the desorption ionization of molecules in a few seconds. The massspectra measured were comparable to mass spectra obtained with thecarrier gas increased to high temperatures (above 300 degreesCentigrade). The mass spectra measured with heated carrier gas requiredseveral minutes before the measurement could be undertaken. In variousembodiments of the invention, using the DART source with roomtemperature carrier gas for analysis of an aliquot of quinine depositedon the mesh was completed in less than 25 seconds by rapidly raising thecurrent passing through the mesh from approximately 0 Amps initially toapproximately 6 Amps. The resulting mass chromatogram (FIG. 4(A)) showsa rapid desorption profile. FIG. 4(B) shows the mass spectrum of the[M+H]⁺ ion region with little or no fragmentation or oxidation. Underconventional DART analyses conditions desorption of quinine requires agas temperature of approximately 300 degrees Centigrade. The spectrafrom experiments carried out with TA-DART revealed similar sensitivityand signal intensity for molecules of interest detected as intactprotonated molecules to those of the conventional DART experiment.

Olive Oil contains predominantly triglycerides with approximate mass of900 Dalton. The TA-DART spectra for Olive Oil revealed an unexpectedresult compared with the conventional DART. The spectrum shown in FIG.5A (with ions at m/z 371.0, 577.8, 603.6, 876.4, 902.4 and 903.4) issimilar to conventional DART analysis of this type of oil, see forexample Vaclavik, L., Cajka, T., Hrbek, V., Hajslova, J., Ambient massspectrometry employing direct analysis in real time (DART) ion sourcefor olive oil quality and authenticity assessment. Analytica ChimicaActa 645 (2009) 56-63, which article is herein explicitly incorporatedby reference in its entirety. FIG. 5A was acquired as the currentapplied to the mesh was at an intermediate value of approximately 4.5Amps. The presence of numerous ions in the mass range from 250-600Dalton can be due to thermal degradation products of the intacttriglycerides. However, as shown in FIG. 5B (with ions at m/z 603.8,604.8 876.4, 902.5, 903.6 and 904.5) a significant decrease in low massions was observed in the TA-DART spectrum when an even higher current ofapproximately 6.5 Amps was applied to the mesh. For example, there was areduction in relative abundance of diglyceride related ions in the500-610 Dalton mass range and the absence of mono-glyceride related ionsin the 250-400 Dalton mass range. The cleaner mass spectrum produced byusing higher current TA-DART can be easier to interpret since thespectrum is dominated by the major intact ions. This result wasconsistently observed even when very high currents were used to generatetemperatures on the wire surface significantly higher than temperaturenormally achieved in conventional DART with a heated carrier gas.

In various embodiments of the invention, TA-DART generates protonatedintact molecules that would normally require a DART carrier gastemperature in excess of approximately 400 degrees Centigrade. Invarious embodiments of the invention, TA-DART can be used to measure aspectrum of a sample in approximately 1/20th of the time required tomeasure a spectrum of a sample with Conventional DART using carrier gasheated to a temperature of approximately 400 degrees Centigrade. Invarious embodiments of the invention, TA-DART results in a significantreduction in the production of ions derived from thermal degradation. Invarious embodiments of the invention, TA-DART can enable a wider fieldof use of DART.

Reducing thermal decomposition of triglycerides has a practicalapplication in the direct analysis of blood for chemicals of interest.DART analysis of blood plasma and whole blood spots for pharmacologicalstudies have produced abundant low mass ions which limited the utilityof the method, see for example Zhao Y., L. M., Wu D., Mak R.,Quantification of small molecules in plasma with direct analysis in realtime tandem mass spectrometry, without sample preparation and liquidchromatographic separation. Rapid Communications in Mass Spectrometry,2008, 22(20): p. 3217-3224 and Yu, S., et al., Bioanalysis withoutSample Cleanup or Chromatography: The Evaluation and InitialImplementation of Direct Analysis in Real Time Ionization MassSpectrometry for the Quantification of Drugs in Biological Matrixes.Analytical Chemistry, 2008. Anal. Chem. 2009, 81, 193-202, both articlesare herein explicitly incorporated by reference in there entireties. Yu,et al., (2008) discloses that the DART source can complete ionization ofsamples by the interaction of the metastable containing carrier gasvaporizing materials from a 1 to 2 μL aliquot of sample applied to theouter surface of a glass melting point capillary (ChemGlass, CG-1841-01)which has been embedded in a formed plastic piece (DIP-it Samplers,IonSense, Inc.) and can be picked up by the action of a customizedautosampler (HTCPAL, LEAP technologies), the AutoDART-96, andsubsequently can be presented to the ionization region of the DART fordesorption. The AutoDART-96 can be programmed to execute a predeterminedseries of movements involving pickup of the sampler, dipping the closedend of the glass tube directly into the plasma, and subsequent sweepingof the glass tube through the ionization region, e.g., at a rate of 500μm per second. The temperature of the DART carrier gas can be set to425° C. to complete effective desorption of the analyte in seconds persample. The DART source can be positioned on a flat table with theAutoDART to permit reproducible desorption ionization. Yu, et al.,(2008) further discloses that utilization of helium gas for desorptionionization with the DART can present the mass spectrometer with therequirement for greater pumping efficiency; however, physicalmodification of the API-4000 with larger pumping capability may not bedesirable. Selective removal of the helium gas from the atmosphericpressure inlet region can be completed by incorporating a new vacuumchamber assembly in front of the normal API inlet and evacuating thatregion with a membrane pump (Vacuubrand, Diaphragm Vacuum Pump MZ 2).The vacuum chamber can be fabricated by modifying the counter currentplate with a ⅛ in. OD pump port. For the experiment, the normal countercurrent drying gas can be eliminated since desolvation of the sample isnot necessary in the DART enabled experiment. An alumina ceramic iontransfer tube (Length 9 in., OD ¼ in., ID 4.75 mm) can be used to closethe gap between the DART source and the API inlet of the massspectrometer, leaving approximately a 2 mm gap between the API-4000skimmer and the ceramic transfer tube inside the vacuum chamber andapproximately a 1 cm sampling gap between the ceramic DART cartridge andthe open end of the ceramic transfer tube. Yu, et al., (2008) furtherdiscloses sample introduction speed and placement at the DART.Specifically, the method of sample introduction at the DART can bevaried to determine the most effective means of sample desorption whileoptimizing sample to sample signal reproducibility. Two differentsampling methods can be programmed to run on the HTCPAL autosampler,AutoDart-96, using LEAP Shell software (LEAP Technologies, Version3.0.1.106). The first sampling method can involve sweeping the DIP-itSampler across the entire sampling region of the DART source (1 cm) at aconstant rate of 500 μm per second. The second sampling method canincorporate a quick movement of the DIP-it Sampler into the center ofthe DART source, a short pause (5 s) with the Dip-it Sampler centered inthe DART beam, and then a quick movement removing the DIP-it Samplercompletely from the DART sampling region. For both sampling methods, theposition of the DIP-it Sampler between the DART cartridge and theceramic transfer tube can be varied in the y and z directions.

Since the mass of many drug candidates is in the same mass region as theproducts of lipid decomposition a reduction in generation of thoseproducts would be especially desirable. The potential that TA-DART mightproduce a simpler mass spectrum from human and animal blood whichcontains triglycerides with greater fatty acid diversity as well assignificant concentration of phosphatidyl-ethanol amines,phosphatidyl-cholines, phosphatidyl-serines and phosphatidyl-inositolscan enable lower detection limits for drug components.

A comparison of the mass spectra from whole blood by conventional DARTand TA-DART confirmed the utility of the TA-DART method for detection ofdrugs in blood. The absence of major ions in the low mass range withTA-DART suggest that many drugs in that mass range can be more easilydetected with greater signal-to-noise.

Another class of thermally sensitive molecules includes pesticides.Fruit can be sampled by rubbing the fruit on a piece of polyethylenefoam material. After sample collection, the piece of foam was positionedbetween the conventional DART source and entry tube of the gas ionseparator attached to the API-MS. Heating the DART carrier gas fromapproximately 150° C.-400° C. required 2 minutes during which time thepesticides collected on the foam were ionized and transferred to themass spectrometer for detection. The pesticides were desorbed over verylong periods of time making quantitation difficult. The thermalproperties of the foam, unlike the mesh, increased the time needed toreach the maximum temperature. Placing a mesh in close proximity to thefoam can allow a more rapid heating of the foam thus facilitating morerapid analysis. FIG. 6 shows a schematic diagram of a sampling systemincorporating a mesh (616) inserted in a holder (690) positioned betweenthe ionizing gas source (601) and porous material (678) upon which thesample to be analyzed is applied, where the porous material (678) ispositioned in close proximity to a gas ion separator (634) which permitstransfer of ions to the API-inlet of the mass spectrometer according tovarious embodiments of the invention. A power supply (660) is used toheat the mesh.

In various embodiments of the invention, the foam sponge plastic 1010shown attached to the wire mesh 1020 applied to a card holder in FIG. 10can be used to contain a solid, liquid or gas/liquid sample. As shown inFIG. 11, a liquid sample can be deposited from a pipette 1140 onto thefoam sponge plastic 1010 shown attached to the wire mesh 1020 associatedwith a card holder 1130. FIG. 13 shows a foam sponge plastic 1010attached to a mesh 1020 associated with a card 1130 mounted on theentrance to a mass spectrometer 1370 positioned between the ionizing gassource 1360 and a gas ion separator (not shown) which permits transferof ions to the API-inlet region of a mass spectrometer (not shown). FIG.14 shows (A) a total ion chromatogram (TIC) over the time interval zeroto two minutes obtained using a carrier gas temperature of 50 degreesCentigrade while rapidly increasing the current passing through the meshsupporting the sample applied to a foam sponge plastic from 0 Amps attime=0, to 6 Amps at time=30 second; (B) a partial mass chromatogram ofthe 195 Dalton ion produced during the two minute analysis shown in FIG.14A; and (C) the mass spectrum (including ions at m/z 217.0 and 233.9)obtained by summing the spectra obtained between 0.68-1.08 minutes ofthe TIC shown in FIG. 14A.

In various embodiments of the invention, a non-conducting porousmaterial is placed between a pair of mesh strips to hold thenon-conducting material positioned immediately between the DART sourceand the API inlet. The current to the mesh can be gradually increased inorder to both implement a source of radiant heat near the non-conductingmaterial (foam) and increase the gas temperature as it passed throughthe mesh.

FIG. 7 shows a schematic diagram of a sampling system incorporating twomeshes (716, 718) with two power supplies (760, 762, only a portion ofthe 760 circuit is shown), wherein the meshes (716, 718) are positionedbetween the ionizing gas source (701) and the sample to be analyzed,where the sample is positioned in close proximity to a gas ion separator(734) which permits transfer of ions to the API-inlet region of the massspectrometer according to various embodiments of the invention.

FIG. 8 shows a schematic diagram of a sampling system incorporating twomeshes (816) with a single power supply (860), wherein the meshes (816)are positioned between the ionizing gas source (801) and the sample tobe analyzed, where the sample is positioned in close proximity to a gasion separator (834) which permits transfer of ions to the API-inletregion of the mass spectrometer according to various embodiments of theinvention. A variable resistor (872) is used to apply different currentsto the two different meshes. The device shown in FIG. 8 enables thepassage of different currents through two or more different meshes inorder to differentially desorb samples from the two or more differentmeshes (816). In various embodiments of the invention, the device shownin FIG. 8 can be used to generate dopant gas to promote ionization ofsample molecules. In various embodiments of the invention, the deviceshown in FIG. 8 can be used to vaporize a reference molecule independentof the sample molecule in order to facilitate accurate mass measurement.In various embodiments of the invention, the device shown in FIG. 8 canbe used to vaporize a reference molecule independent of the samplemolecule in order to perform quantitation of the sample molecule. Thevariable resistor 872 can be used to adjust the current thus permittingmore accurate adjustment of the temperature applied to the second mesh.In various embodiments of the invention, the device shown in FIG. 8 canbe used to vaporize a reference molecule independent of the samplemolecule in order to determine a correlation between current applied andtemperature on the mesh so that the current applied to the second meshcan be adjusted to a specific temperature.

In various embodiments of the invention, two wire mesh 1520 and 1522associated with a card 1530 as shown in FIG. 15 can be heated by asingle power supply (not shown) and used to analyze a sample. FIG. 18shows (the side perspective) of the two mesh 1520 and 1522 associatedwith a card 1530 from FIG. 15 mounted on the entrance to a massspectrometer 1370, between the distal end of the ionizing source 1360and the API-inlet region 1750. FIG. 19 shows the mass spectrum (withions at m/z 603.4, 902.4 and 918.1) obtained from a sample of a solutioncontaining 1% olive oil dissolved in toluene an aliquot of which isapplied to the first mesh placed between the distal end of the ionizingsource and a second mesh to which a solution of ammonia was applied,wherein both mesh are associated with a card configured to permitheating by a single power supply. For comparison, FIG. 20 shows the massspectrum (with ions at m/z 339.6, 603.8, 876.7 and 902.4) obtained fromanalysis of an aliquot of olive oil dissolved in toluene applied to asingle mesh associated with a card which was heated by a power supply.The use of ammonia as a dopant (see FIG. 19) increased the formation ofthe ammonia adduct of the triglycerides while decreasing the abundanceof the protonated molecules (not intense) (see FIG. 20).

FIG. 9A shows a schematic diagram of a sampling system incorporating acard (999) with a cut out region (998), and a reservoir (994) whereinone or more tubes (990, 992, 996) are associated with the reservoir(994) and the card (999) is positioned between an ionizing gas source(901) and a gas ion separator (934) which permits transfer of ions tothe API-inlet region of the mass spectrometer according to variousembodiments of the invention. In various embodiments of the invention, asample can be introduced into the reservoir (994) through one or moretubes (990, 992) to allow for liquid analysis transmission mode DART. Invarious embodiments of the invention, a filament or a mesh (not shown)can be positioned associated with the card (999) at the cut our region(998). In alternative embodiments of the invention, no filament or meshis associated with the cut our region (998) and the gaseous sampleinteracts with the ionizing species in the cut out region (998). Asample in the reservoir (994) can be introduced into the cut out region(998) through a tube (996). In various embodiments of the invention, thedevice shown in FIG. 9A can be used to introduce a solid, liquid orgaseous sample from the reservoir (994) for desorption and ionization.In various embodiments of the invention, the device shown in FIG. 9A canbe used to continuously introduce a liquid sample for desorption andionization. In embodiments of the invention, a filament positioned inthe cut out region (998) can be used to create a potential differencebetween a conducting tube (996) to electrospray the sample into the cutout region (998). In various embodiments of the invention, the deviceshown in FIG. 9A can be used to apply a current at regular intervals toa mesh associated with the cut out region (998) to enable the periodicdesorption of introduced liquid or gaseous samples. In variousembodiments of the invention, in the device shown in FIG. 9A, the tube(990) can be coupled to a liquid chromatography system for desorptionand ionization of the analytes eluted off the chromatographic material(994). In alternative embodiments of the invention, the chromatographycan be accomplished prior to introduction of the stream onto the cardand the volume of the reservoir minimized to the volume of the tubing(990, 992, 996).

In various embodiments of the invention, the reservoir shown in FIG. 9Acan be depressed by the application of a trigger (991) to the reservoir(994) as shown in FIGS. 9B-9D. In various embodiments of the invention,by sealing or using a one way valve to stop flow through theintroduction tube (see 990, 992 in FIG. 9A), the trigger (991) appliespressure to a flexible reservoir which dispenses the solution or vaporthrough tube (996) into the cut out region (998) of the card (999) (seeFIGS. 9B-9D). The flexible reservoir can be made of rubber or a varietyof plastics with sufficient elasticity to allow perturbation to deliverthe solution or vapor. In various embodiments of the invention, theflexible reservoir can allow reloading of a sample after the solution orvapor has been delivered. In another embodiment of the invention, thereservoir is static and relies upon the application of electric fieldsor electro hydrodynamic pressure to deliver a solution through the tube(996).

In various embodiments of the invention, a series of different meshstrips through which different currents can be directed permitscollection of multiple mass spectra from the same sample at differenttemperatures. This configuration can be desirable in order to avoidheating the sample too rapidly resulting in the rapid desorption of lowmass, or more volatile molecules.

In various embodiments of the invention increasing the density of themesh positioned between the source and proximal end of the gas ionseparator results in a reduction in the number of ions related to theatmosphere surrounding the sample being detected. Analysis of sampleswith mesh positioned between the source and API-inlet also decreases theabundance of ions from the ambient air which normally contributessignificant background to the mass spectrum. The reduction in backgroundrelative to production of sample related ions improves thesignal-to-noise resulting in an increase in the sensitivity of the DARTtechnique when using the mesh as a sample containment device.

In various embodiments of the invention, a mesh includes two or morecomponents in physical contact selected from the group consisting of twoor more connected wires or two or more connected strings, foam,polymers, silica, cellulose, and hydrophobic support material. Invarious embodiments of the invention, a mesh includes two or morecomponents physically bound together selected from the group consistingof two or more connected wires or two or more connected strings, foam,polymers, silica, cellulose, and hydrophobic support material.

In various embodiments of the invention, a mesh can be contacted withthe analyte and can then be analyzed. In various embodiments of theinvention, a mesh can be in the spatial vicinity of the analyte, themesh can be heated and the analyte analyzed.

In various embodiments of the invention, the heating of the mesh can beeffected through the use of an infra-red (IR) laser. In variousembodiments of the invention, the heating of the mesh can beaccomplished by directing an IR laser onto specific sites on a mesh. TheIR laser frequency can be absorbed by water molecules and the energyconverted into heat to effect the desorption of the analyte.

In various embodiments of the invention, the heating or cooling of themesh can be affected through the conductive transfer of heat from a heatsink. The temperature of the heat sink can be adjusted by transfer ofelectric current to the heat sink. The temperature of the heat sinkwhich is located in the vicinity of the analyte applied to the mesh canthen be used to adjust the temperature of the analyte.

In various embodiments of the invention, the heating of the mesh can beaffected when in proximity to a radiant heat source such as a filamentwith an electric current passing through the filament.

In various embodiments of the invention, heating the mesh may be used tofacilitate reactions of one or more analyte, the products of whichreactions can be analyzed and can be used to infer the actual identityor quantity of the one or more analytes. In various embodiments of theinvention, the mesh can be mounted on a card which can be used toisolate the analyte from contaminants, facilitating handling of thesample. In various embodiments of the invention, the material of thecard is capable of absorbing or otherwise retaining and releasing achemical to be used as a dopant to assist ionization at room temperatureor after application of heat to vaporize the analyte or product. Invarious embodiments of the invention, the mesh is in the shape of acylinder or tube of variable diameter and size, wherein liquid or solidsample is placed into the cylinder or tube through an opening. Invarious embodiments of the invention, the mesh is shaped like a“bowtie,” with a thin spot in the middle and two ends that increase inwidth as they extend outward away from the center. In variousembodiments of the invention, the mesh is in the shape of a “trough,”with mesh for the bottom and two sides and an opening in the top withwhich to hold loose chemicals, leaves, pulverized materials, soil,cells, or solid particles for analysis. In various embodiments of theinvention, a mesh trough 2124 associated with a card 2130 can be heatedby a single power supply (not shown) and used to analyze a sample (seeFIG. 21). FIG. 12 shows Oolong tea leaves 2280 held in a mesh trough2124 associated with a card 2130 which can be heated by a power supply(not shown) according to an embodiment of the invention. FIG. 16 showsthe mass spectrum (with ions at m/z 195.2, 200.3, 369.3, 391.0 and419.0) obtained from a sample of Oolong tea leaves enclosed in a meshtrough associated with a card which was heated by a power supplyaccording to an embodiment of the invention. FIG. 17 shows aconventional DART mass spectrum (with ions at m/z 195.2, 216.9 and390.9) obtained from a sample of Oolong tea leaves. Comparison of theresults generated by using the two approaches shows an increase thenumber and abundance of ions representative of the sample that have beengenerated using the greater sampling capacity of the mesh trough.

In various embodiments of the invention, a filament can be deployed witha card. In various embodiments of the invention, a mesh can be deployedwith a card. By deploying the mesh with a card, the card can be held bythe user while a sample can be applied to the mesh without the sample orthe mesh being contaminated by the user.

In various embodiments of the invention, a reservoir capable of holdinga gas or liquid can be deployed with a card. In various embodiments ofthe invention, a reservoir capable of holding a gas or liquid can bedeployed in the vicinity of a mesh with a card. One or more tubes can beassociated with the reservoir. One of the one or more tubes can be usedfor filling the reservoir with a liquid or gas sample. One or more tubescan be orientated towards a mesh. The reservoir can be filed orpartially filed with a gas or solvent prior to insertion of the cardinto an instrument for analysis. The liquid or gas in the reservoir canbe partially or fully expelled by the action of a force on the reservoirthrough the one or more tubes. The one or more tubes which can expel theliquid or gas can include a tube upon which an electrical potential canbe applied to the tube. Applying the electrical potential to the tubecan induce the liquid or gas to exit the reservoir. The tube exiting thereservoir can be orientated towards a mesh or a filament.

A device for analyzing an analyte comprising a spectrometer including anentrance for analyzing the analyte and a source including a proximal endand a distal end configured for generating ionizing species, where thedistal end is proximal to the spectrometer entrance, where anatmospheric pressure region is located between the distal end of thesource and the spectrometer entrance. The device further comprising asupply adapted to one or more of generate, transfer, conduct and radiateheat and one or more mesh positioned in the atmospheric pressure region,where the analyte is applied on or near the one or more mesh, where thesupply can one or more of generate, transfer, conduct and radiate heatto the analyte, where analyte molecules desorbed from the one or moremesh interact with the ionizing species generated by the source to forma plurality of analyte ions which enter the spectrometer.

A device for analyzing an analyte which comprises a spectrometerincluding a proximal end and a distal end configured for analyzing theanalyte, where an entrance for the analyte is located at the proximalend and a detector is located at the distal end, where an atmosphericpressure region is maintained through the length of the spectrometerbetween the proximal end and the distal end. The device furthercomprising a source including a proximal end and a distal end configuredfor generating ionizing species, where the distal end of the source isproximal to the spectrometer entrance, where an atmospheric pressureregion is located between the proximal end of the source and the distalend of the source and extends to the proximal end of the spectrometer.The device further comprising a supply adapted to one or more ofgenerate, transfer, conduct and radiate heat and one or more meshpositioned in the atmospheric pressure region, where the analyte isapplied on or near the one or more mesh at the proximal end of thesource, where the supply can one or more of generate, transfer, conductand radiate heat to the analyte, where analyte molecules desorbed fromthe one or more mesh interact with the ionizing species generated by thesource to form a plurality of analyte ions which enter the spectrometer.

In various embodiments of the invention, the source operates by atechnique selected from the group consisting of electrospray ionization,nano-electrospray ionization, atmospheric pressure matrix-assisted laserdesorption ionization, atmospheric pressure chemical ionization,desorption electrospray ionization, atmospheric pressure dielectricbarrier discharge ionization, atmospheric pressure low temperatureplasma desorption ionization, and electrospray-assisted laser desorptionionization, a direct analysis real time, plasma assisteddesorption/ionization, dielectric barrier discharge ionization source,desorption atmospheric pressure chemical ionization, desorption sonicspray ionization, desorption atmospheric pressure photoionization, andflowing atmospheric-pressure afterglow, an atmospheric laser desorptionionization, a Corona discharge, an inductively coupled plasma and a glowdischarge source.

In various embodiments of the invention, the spectrometer is selectedfrom the group consisting of a mass spectrometer, a handheld massspectrometer, an ion mobility spectrometer (IMS) and a handheld IMS. Invarious embodiments of the invention, the spectrometer is selected fromthe group consisting of a quadrupole ion trap, a rectilinear ion trap, acylindrical ion trap, a ion cyclotron resonance trap, an orbitrap, asector, and a time of flight mass spectrometer.

In an embodiment of the invention, a device for analyzing an analytecomprises a spectrometer configured for analyzing the analyte, with anentrance for accepting analyte ions, a detector for detecting analyzedanalyte ions and an atmospheric pressure source configured forgenerating ionizing species. The device further comprises a flow of theanalyte molecules or clusters of analyte and solvent molecules from asolution where the analyte molecules or clusters of analyte and solventmolecules interact with the ionizing species generated by the source toform a plurality of analyte ions which enter the spectrometer and areanalyzed. The flow of the analyte molecules or clusters of analyte andsolvent molecules can be generated by one or more techniques includingmatrix assisted laser desorption, secondary ion impact techniques,electrospray, thermospray and electro-hydrodynamic desorption. Prior toforming the flow of analyte molecules or clusters of analyte and solventmolecules, the analyte can be chromatographically separated byinteracting with a solid support.

A device for analyzing an analyte comprises an ion mobility spectrometerincluding an entrance and a detector with a first potential applied tothe ion mobility spectrometer entrance, a source configured forgenerating ionizing species, a supply adapted to one or more of generateheat, transfer heat, conduct heat, radiate heat and apply an electricpotential, and two or more mesh positioned between the source and thespectrometer. The analyte is applied on or near a first mesh, where thesupply can one or more of generate heat, transfer heat, conduct heat andradiate heat to the analyte to desorb molecules of the analyte, wheremolecules desorbed from the first mesh interact with the ionizingspecies generated by the source to form analyte ions. The device wherethe mesh on which the analyte is applied is grounded. The device wherethe mesh on which the analyte is applied does not have the firstpotential. The device where the mesh on which the analyte is applied hasa potential that is approximately 100 volts different than the firstpotential. The device where the mesh on which the analyte is applied hasa potential that is approximately 1000 volts different than the firstpotential. The two or more mesh have two or more potentials, where thetwo or more potential are approximately 100 volts different than thefirst potential. The two or more mesh have two or more potentials, wherethe two or more potential are approximately 1000 volts different thanthe first potential.

In various embodiments of the invention, the analyte is of at least onestate selected from the group consisting of solid phase, liquid phase,and gas phase. In various embodiments of the invention, the analyte isof biological origin. In various embodiments of the invention, theanalyte is of non-biological origin. In various embodiments of theinvention, the analyte is selected from the group consisting of anindustrial work piece, a pharmaceutical product, a pharmaceuticalingredient, a food, a food ingredient, a toxin, a drug, an explosive, abacterium, and a biological tissue.

While the systems, methods, and devices have been illustrated bydescribing examples, and while the examples have been described inconsiderable detail, it is not the intention of the applicants torestrict or in any way limit the scope of the appended claims to suchdetail. It is, of course, not possible to describe every conceivablecombination of components or methodologies for purposes of describingthe systems, methods, and devices provided herein. Additional advantagesand modifications will readily be apparent to those skilled in the art.Therefore, the invention, in its broader aspects, is not limited to thespecific details, the representative system, method or device, andillustrative examples shown and described. Accordingly, departures maybe made from such details without departing from the spirit or scope ofthe applicant's general inventive concept. Thus, this application isintended to embrace alterations, modifications, and variations that fallwithin the scope of the appended claims. Furthermore, the precedingdescription is not meant to limit the scope of the invention. Rather,the scope of the invention is to be determined by the appended claimsand their equivalents.

What is claimed is:
 1. A device comprising: one or more mesh; an analytedeployed on a plastic in proximity to the one or more mesh; a supply togenerate heat at the one or more mesh; an autosampler, where theautosampler is used to contact the plastic with the analyte; and anatmospheric pressure source configured to direct an ionizing species atthe plastic to generate one or more analyte ions.
 2. The device of claim1, further comprising a gas ion separator positioned distal to the oneor more mesh and distal to the atmospheric pressure source.
 3. Thedevice of claim 1, wherein the atmospheric pressure source is selectedfrom the group consisting of a direct analysis real time (DART), PlasmaAssisted Desorption/Ionization (PADI), Dielectric Barrier Dischargeionization source (DBDI or DCBI), Desorption Atmospheric PressureChemical Ionization (DAPCI), Desorption Sonic Spray Ionization (DeSSI),Desorption Atmospheric Pressure Photoionization (DAPPI), and FlowingAtmospheric-Pressure Afterglow (FAPA) and a desorption electrosprayionization (DESI), an atmospheric laser desorption ionization, a Coronadischarge, an inductively coupled plasma (ICP) and a glow dischargesource.
 4. The device of claim 1, where the supply is adapted to delivera power to one of the one or more mesh of between: a lower limit ofapproximately 10² Watts; and an upper limit of approximately 10³ Watts.5. The device of claim 1, where the supply applies a current at regularintervals to at least one of the one or more mesh.
 6. The device ofclaim 1, where a solution containing the analyte contacts the plastic.7. The device of claim 6, further comprising a spectrometer to analyzethe one or more analyte ions.
 8. The device of claim 1, furthercomprising where the autosampler is used to introduce the plastic inproximity to the one or more mesh.
 9. The device of claim 1, where theplastic is a sponge plastic.
 10. The device of claim 1, where theplastic is a plastic foam.
 11. The device of claim 1, where the ionizingspecies are generated at least in part by heating a gas to generate theionizing species.
 12. The device of claim 1, where the analyte is one orboth a liquid and a solid.
 13. The device of claim 1, where the plasticcomprises teflon.
 14. A device comprising: a mesh; an analyte deployedon a plastic sampling tip positioned in close proximity to the mesh; asupply to pass a current through the mesh; an autosampler, where theautosampler is used to contact the plastic sampling tip with theanalyte, where the autosampler is used to introduce the plastic samplingtip in proximity to the mesh: and an atmospheric pressure sourceconfigured to direct an ionizing species at the plastic sampling tip.15. The device of claim 14, where the ionizing species are generated atleast in part by heating a gas to generate the ionizing species.
 16. Thedevice of claim 14, where the analyte is one or both a liquid and asolid.
 17. The device of claim 14, where the plastic sampling tipcomprises teflon.
 18. A device comprising: a mesh; an analyte deployedon a sample tube positioned in close proximity to the mesh, where thesample tube is positioned near the mesh using an autosampler; a supplyto pass a current through the mesh; and an atmospheric pressure sourceconfigured to direct an ionizing species at the sample tube.
 19. Thedevice of claim 18, where the sample tube is inserted into a solution ofthe analyte.
 20. The device of claim 18, where the analyte is one orboth a liquid and a solid.